EARLY TREATMENT OF MENKES DISEASE WITH PARENTERAL COOPER-HISTIDINE - LONG-TERM FOLLOW-UP OF 4 TREATED PATIENTS

We report on the long-term clinical course of 4 boys with Menkes disea se, treated from early infancy with parenteral copper-histidine, with follow-up over 10-20 years, Three of the 4 had male relatives with a s evere clinical course compatible with classical Menkes disease, As a c onsequence of early treatment, our patients have normal or near-normal intellectual development, but have developed many of the more severe somatic abnormalities of the related disorder, occipital horn syndrome , including severe orthostatic hypotension in 2, In addition, 1 boy de veloped a previously unreported anomaly, namely, massive splenomegaly and hypersplenism as a consequence of a splenic artery aneurysm, Previ ously reported molecular studies in 2 of these patients had shown gene defects which would have predicted a truncated and probably nonfuncti onal gene product, Despite the favorable effects on the neurological s ymptoms, parenteral copper treatment for Menkes disease should still b e regarded as experimental, The development of more effective treatmen ts must await a more precise delineation of the role which the Menkes protein plays in intracellular copper trafficking. (C) 1998 Wiley-Liss , Inc.